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Possible involvement of a gamma-hydroxybutyric acid receptor in startle disease
M Berthier1, D Bonneau, J M Desbordes
1Services de Pédiatrie, de Génétique Médicale et d'Anesthésiologie, Centre Hospitalier Universitaire de Poitiers, France.
Insights
Startle disease, a neurological disorder, involves low gamma-aminobutyric acid (GABA) levels. Treatments targeting GABA pathways, including gamma-hydroxybutyrate (GHB), showed no improvement, suggesting other mechanisms may be involved.
Area of Science:
- Neurology
- Neurochemistry
Background:
- Startle disease (hyperekplexia) is an autosomal dominant neurological disorder.
- Characterized by neonatal onset, muscular hypertonia, and exaggerated startle responses.
- Previous studies noted low cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) in affected infants.
Observation:
- A newborn with startle disease presented with low CSF GABA concentrations.
- Treatment with progabide, a GABA agonist, did not yield clinical improvement.
- High-dose gamma-hydroxybutyrate (GHB), a GABA analogue, failed to alleviate muscular stiffness or induce anesthesia.
Findings:
- The lack of response to GABA-ergic agents suggests GABA pathways may not be the primary cause of startle disease.
- The ineffectiveness of GHB implies that its specific receptors, distinct from GABA receptors, might be implicated.
Implications:
- These findings challenge the current understanding of startle disease pathophysiology.
- Further research into novel GHB receptors could reveal new therapeutic targets for startle disease.
- This study highlights the complexity of neurological disorders and the need for personalized treatment approaches.
Abstract:
Startle disease or hyperreflexia is an autosomal dominant neurological disorder, with a neonatal onset, characterized by muscular hypertonia and myoclonic jerks, exaggerated by the slightest stimulus. Low concentrations of free gamma-aminobutyric acid (GABA) have been found in the cerebrospinal fluid of two affected infants. The involvement of GABA or its receptors has been raised and the use of GABA-agonist drugs has been suggested. We report a newborn with startle disease who also had a low concentration of GABA in the cerebrospinal fluid. No clinical improvement was observed with progabide, a GABA agonist. Furthermore, a high dose (100 mg/kg) of gamma-hydroxybutyrate (GHB) did not improve muscular stiffness and failed to induce general anesthesia. GHB, currently used as an effective general anaesthetic, is a structural analogue of GABA. It is present naturally at low concentrations in the brain and is regarded as an inhibitory neurotransmitter. Two specific GHB receptors, distinct from the GABA receptors, have been identified in rat brain. Failure to induce general anesthesia with a high dose of GHB suggests that one of these receptors could be involved in startle disease.